The tuberculin skin test in relation to immunologicalin vitroreactions in BCG-vaccinated healthcare workers

Abstract

The aim was to study the tuberculin skin test in relation to immunological in vitro reactions in bacille Calmette-Guérin (BCG)-vaccinated healthcare workers.The present study was performed in Sweden, a country with a low incidence of tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion rates. BCG-vaccinated healthcare workers (n~381) were tuberculin skin tested. From these, 11 subjects with negative tuberculin reactions (v6 mm) were matched for age and sex with 11 subjects with large positive reactions (¢15 mm). Lymphocyte transformation and the production of interferon-gamma (IFN-c) were analysed after stimulation in vitro of peripheral blood mononuclear cells with tuberculin purified protein derivative, heatkilled tubercle bacilli and a culture filtrate from tubercle bacilli.In the tuberculin-positive group the lymphocyte transformation response was 2-3 times larger, and IFN-c production was 7-10 times larger, than in the tuberculinnegative group (pv0.001).The present results suggest that a positive tuberculin skin test in bacille CalmetteGuérin-vaccinated subjects indicates a stronger immune response of the protective T-helper 1-type than does a negative test. In similar settings, the study supports the traditional practice of regarding the tuberculin skin test in bacille CalmetteGuérin-vaccinated subjects as an indicator of a protective immune response against tuberculosis.

Vacina BCG: via percutânea ou intradérmica?

“…29,38 This is no longer true when BCG vaccine responses are evaluated in individuals who live in communities that are heavily exposed to M. tuberculosis or other mycobacteria, such as in Africa (Malawi).…”

“…4,7,27,28 The United States, Japan and some European countries have adopted the BCG-PC technique because of the ease of administration and the lower number of adverse reactions even though adverse events are very rare in association with BCG-ID. 4,9,10,16,29,30 In England, 95% of babies vaccinated with BCG-ID exhibited scarring in contrast with 63% of those vaccinated with BCG-PC. The intradermal technique was considered difficult by 35% of doctors and, since DTH skin test response results were similar for both groups (68% and 73%, respectively), they concluded that BCG-PC had a greater acceptance for large-scale use.…”

“…6,19 In the USA and United Kingdom, where the BCG-PC vaccine has been adopted, there are low incidences of tuberculosis and the disease is not considered a significant public health problem. 13,14,16,[29][30][31][32][33] In Japan, despite the BCG-PC vaccine being widely used, the incidence of tuberculosis is even lower than in the USA and there is currently debate on the need to maintain the vaccination program. 15,34 The studies of BCG-PC published in these countries, therefore, do not provide any data on the effectiveness of the vaccine.…”

“…Studies performed on experimental animals and on humans demonstrated that DTH skin test response has no relationship with protection and that individuals who react strongly to PPD may be less well protected against tuberculosis compared to those who do not exhibit a positive DTH skin test response. 21,29,31,37 Furthermore the post vaccination response to tuberculin testing is highly variable, depending on the strength of the vaccine employed, the strain, the age at which vaccination took place and the time that has passed since vaccination. 18,21,28 Therefore, new methods are needed to evaluate the capacity of BCG vaccines to stimulate protective immunoresponses.…”

“…An analysis of comparative studies of BCG-ID and BCG-PC leads to the following conclusions: stimulation of a DTH skin test response and the production of cytokines associated with Th1 lymphocytes are more reliable with BCG-ID; 4,12,49 low dosages of the BCG vaccine are unreliable for inducing protective responses, as assessed by IF-γ production; 42 it is probable that the differences between the results found when comparing the two techniques are the result of the lower dosage inoculated percutaneously; [6][7][8][9][30][31][32][33][34][35][36][37][38][39][40][41][42] adverse events associated with BCG are most common in association with poor administration technique; 4,9,18 the use of scarring to test whether the vaccine has taken is only of use after BCG-ID since BCG-PC does not leave scars; 9,18,19 the presence of scars should be verified during infancy since the scar reduces in size over the years; 27,29 BCG-ID gives better protection against the more severe forms of the disease, which principally occur d u r i n g c h i l d h o o d , s u c h a s m e n i n g i t i s tuberculosa; 2,3,32,33,35 to date, there is no evidence to prove that revaccination is effective for increasing the levels of protection against tuberculosis afforded to adolescents and adults. 28,33,41,47 Recommendations In Brazil, increased vaccination coverage with BC...…”